Publications by authors named "Kui Li"

447 Publications

Landscape of tissue-specific RNA Editome provides insight into co-regulated and altered gene expression in pigs ().

RNA Biol 2021 Jul 27:1-12. Epub 2021 Jul 27.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

RNA editing generates genetic diversity in mammals by altering amino acid sequences, miRNA targeting site sequences, influencing the stability of targeted RNAs, and causing changes in gene expression. However, the extent to which RNA editing affect gene expression via modifying miRNA binding site remains unexplored. Here, we first profiled the dynamic A-to-I RNA editome across tissues of Duroc and Luchuan pigs. The RNA editing events at the miRNA binding sites were generated. The biological function of the differentially edited gene in skeletal muscle was further characterized in pig muscle-derived satellite cells. RNA editome analysis revealed a total of 171,909 A-to-I RNA editing sites (RESs), and examination of its features showed that these A-to-I editing sites were mainly located in SINE retrotransposons PRE-1/Pre0_SS element. Analysis of differentially edited sites (DESs) revealed a total of 4,552 DESs across tissues between Duroc and Luchuan pigs, and functional category enrichment analysis of differentially edited gene (DEG) sets highlighted a significant association and enrichment of tissue-developmental pathways including TGF-beta, PI3K-Akt, AMPK, and Wnt signaling pathways. Moreover, we found that RNA editing events at the miRNA binding sites in the 3'-UTR of mRNA could prevent the miRNA-mediated mRNA downregulation of in the muscle-derived satellite (MDS) cell, consistent with the results obtained from the Luchuan skeletal muscle. This study represents the most systematic attempt to characterize the significance of RNA editing in regulating gene expression, particularly in skeletal muscle, constituting a new layer of regulation to understand the genetic mechanisms behind phenotype variance in animals.
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http://dx.doi.org/10.1080/15476286.2021.1954380DOI Listing
July 2021

Differing susceptibility of C57BL/6J and DBA/2J mice-parents of the murine BXD family, to severe acute respiratory syndrome coronavirus infection.

Cell Biosci 2021 Jul 19;11(1):137. Epub 2021 Jul 19.

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.

The ongoing coronavirus disease-2019 (COVID-19) pandemic, caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that is closely related to SARS-CoV, poses a grave threat to global health and has devastated societies worldwide. One puzzling aspect of COVID-19 is the impressive variation in disease manifestations among infected individuals, from a majority who are asymptomatic or exhibit mild symptoms to a smaller, largely age-dependent fraction who develop life-threatening conditions. Some of these differences are likely the consequence of host genetic factors. Systems genetics using diverse and replicable cohorts of isogenic mice represents a powerful way to dissect those host genetic differences that modulate microbial infections. Here we report that the two founders of the large BXD family of mice-C57BL/6J and DBA/2J, differ substantially in their susceptibility to a mouse-adapted SARS-CoV, MA15. Following intranasal viral challenge, DBA/2J develops a more severe disease than C57BL/6J as evidenced by more pronounced and sustained weight loss. Disease was accompanied by high levels of pulmonary viral replication in both strains early after infection but substantially delayed viral clearance in DBA/2J. Our data reveal that the parents of the BXD family are segregated by clear phenotypic differences during MA15 infection and support the feasibility of using this family to systemically dissect the complex virus-host interactions that modulate disease progression and outcome of infection with SARS-CoV, and provisionally also with SARS-CoV-2.
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http://dx.doi.org/10.1186/s13578-021-00656-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287544PMC
July 2021

SINE jumping contributes to large-scale polymorphisms in the pig genomes.

Mob DNA 2021 Jun 28;12(1):17. Epub 2021 Jun 28.

College of Animal Science & Technology, Yangzhou University, 225009, Yangzhou, Jiangsu, China.

Background: Molecular markers based on retrotransposon insertion polymorphisms (RIPs) have been developed and are widely used in plants and animals. Short interspersed nuclear elements (SINEs) exert wide impacts on gene activity and even on phenotypes. However, SINE RIP profiles in livestock remain largely unknown, and not be revealed in pigs.

Results: Our data revealed that SINEA1 displayed the most polymorphic insertions (22.5 % intragenic and 26.5 % intergenic), followed by SINEA2 (10.5 % intragenic and 9 % intergenic) and SINEA3 (12.5 % intragenic and 5.0 % intergenic). We developed a genome-wide SINE RIP mining protocol and obtained a large number of SINE RIPs (36,284), with over 80 % accuracy and an even distribution in chromosomes (14.5/Mb), and 74.34 % of SINE RIPs generated by SINEA1 element. Over 65 % of pig SINE RIPs overlap with genes, most of them (> 95 %) are in introns. Overall, about one forth (23.09 %) of the total genes contain SINE RIPs. Significant biases of SINE RIPs in the transcripts of protein coding genes were observed. Nearly half of the RIPs are common in these pig breeds. Sixteen SINE RIPs were applied for population genetic analysis in 23 pig breeds, the phylogeny tree and cluster analysis were generally consistent with the geographical distributions of native pig breeds in China.

Conclusions: Our analysis revealed that SINEA1-3 elements, particularly SINEA1, are high polymorphic across different pig breeds, and generate large-scale structural variations in the pig genomes. And over 35,000 SINE RIP markers were obtained. These data indicate that young SINE elements play important roles in creating new genetic variations and shaping the evolution of pig genome, and also provide strong evidences to support the great potential of SINE RIPs as genetic markers, which can be used for population genetic analysis and quantitative trait locus (QTL) mapping in pig.
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http://dx.doi.org/10.1186/s13100-021-00246-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240389PMC
June 2021

Gapless indica rice genome reveals synergistic contributions of active transposable elements and segmental duplications to rice genome evolution.

Mol Plant 2021 Jun 23. Epub 2021 Jun 23.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Shenzhen Research Institute of Nanjing University, Shenzhen 518000, China. Electronic address:

The ultimate goal of genome assembly is a high-accuracy gapless genome. Here, we report a new assembly pipeline that is used to produce a gapless genome for the indica rice cultivar Minghui 63. The resulting 397.71-Mb final assembly is composed of 12 contigs with a contig N50 size of 31.93 Mb. Each chromosome is represented by a single contig and the genomic sequences of all chromosomes are gapless. Quality evaluation of this gapless genome assembly showed that gene regions in our assembly have the highest completeness compared with the other 15 reported high-quality rice genomes. Further comparison with the japonica rice genome revealed that the gapless indica genome assembly contains more transposable elements (TEs) and segmental duplications (SDs), the latter of which produce many duplicated genes that can affect agronomic traits through dose effect or sub-/neo-functionalization. The insertion of TEs can also affect the expression of duplicated genes, which may drive the evolution of these genes. Furthermore, we found the expansion of nucleotide-binding site with leucine-rich repeat disease-resistance genes and cis-zeatin-O-glucosyltransferase growth-related genes in SDs in the gapless indica genome assembly, suggesting that SDs contribute to the adaptive evolution of rice disease resistance and developmental processes. Collectively, our findings suggest that active TEs and SDs synergistically contribute to rice genome evolution.
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http://dx.doi.org/10.1016/j.molp.2021.06.017DOI Listing
June 2021

Measurement of the Brain Volume/Liver Volume Ratio by Three-Dimensional MRI in Appropriate-for-Gestational Age Fetuses and Those With Fetal Growth Restriction.

J Magn Reson Imaging 2021 Jun 21. Epub 2021 Jun 21.

Department of Radiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Fetal growth restriction (FGR) is associated with a high fetal brain volume/liver volume (FBV/FLV) ratio. Ultrasound may not always be reliable, which has prompted further investigation of MRI techniques.

Purpose: To determine the relationship between FBV/FLV ratio, as measured by MRI, and gestational age (GA) in normal fetuses and those with FGR.

Study Type: Retrospective.

Population: One hundred and forty seven singleton pregnancies including 105 appropriate-for-gestational age (AGA) fetuses and 42 FGR fetuses.

Field Strength/sequence: Three-dimensional fast imaging employing steady-state acquisition at 1.5 T.

Assessment: The FBV and FLV were measured by three radiologists. The inter- and intraobserver agreements, the correlation between FBV/FLV ratio, and advancing GA were evaluated; the diagnostic value of FBV/FLV ratio was evaluated and compared with head circumference/abdominal circumference (HC/AC) ratio measured by ultrasound.

Statistical Tests: Intraclass correlation coefficient (ICC) was used to determine inter- and intraobserver agreements. Regression analysis was used to assess the correlation between FBV/FLV ratio and advancing GA. The diagnostic value of the FBV/FLV ratio was examined by the area under the receiver operating characteristic (ROC) curve.

Results: The inter- and intraobserver agreements were excellent with an interobserver ICC of 0.984 and intra-observer ICCs of 0.989, 0.994, and 0.995. The FBV/FLV ratio in AGA fetuses decreased significantly with advancing GA (Pearson correlation coefficient = -0.844). The FBV/FLV ratio in FGR fetuses was significantly higher than that in AGA fetuses. To identify fetuses at high risk for FGR using the FBV/FLV ratio, the area under the ROC curve was 0.978, with an optimal cut-off value of 4.10. The sensitivity of FBV/FLV ratio in identifying FGR was significantly higher than that of HC/AC ratio (0.929 vs. 0.529).

Data Conclusion: An inverse correlation exists between FBV/FLV ratio and advancing GA in normal fetuses. A high FBV/FLV ratio may be used to ascertain fetuses at high risk for FGR.

Level Of Evidence: 3 Technical Efficacy Stage: 3.
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http://dx.doi.org/10.1002/jmri.27792DOI Listing
June 2021

Diffusion MRI Based Myometrium Tractography for Detection of Placenta Accreta Spectrum Disorder.

J Magn Reson Imaging 2021 Jun 21. Epub 2021 Jun 21.

Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.

Background: Prenatal diagnosis of placenta accreta spectrum (PAS) disorders is difficult. Magnetic resonance imaging (MRI) has been shown to be a useful supplementary method to ultrasound.

Purpose: To investigate diffusion MRI (dMRI) based tractography as a tool for detecting PAS disorders, and to evaluate its performance compared with anatomical MRI.

Study Type: Prospective.

Population: Forty-seven pregnant women in the third trimester with risk factors for PAS.

Field Strength/sequence: Using fast imaging employing steady-state acquisition and high-angular resolution dMRI at 1.5 Tesla.

Assessment: Diagnosis of PAS was performed by three radiologists based on the dMRI-based feature of myometrial fiber discontinuity and on commonly used anatomical features including presence of dark band, discontinuous myometrium and bladder wall interruption. We evaluated the sensitivity, specificity, accuracy, and area-under-the-curve (AUC) of the individual features and established an integrated model with random forest analysis.

Statistical Tests: Maternal age and gestational age at scan were compared between PAS and control group using a t-test, and childbearing history was compared using a chi-squared test. The random forest model was employed to combine the anatomical and dMRI features with 5-fold cross-validation, and the weight of each feature was normalized to evaluate its importance in predicting PAS.

Results: Based on surgical pathology reports, 16 out of 47 patients had confirmed PAS. The anatomical feature of dark bands and tractography marker achieved the highest AUC of 0.842 for predicting PAS, and the integrated anatomical and tractography features further improved the AUC of 0.880 with an accuracy of 87.2%. The tractography feature contributed most (30.1%) to the integrated model.

Data Conclusion: Myometrial tractography demonstrated superior performance in detecting PAS. Moreover, the combination of dMRI-based tractography and anatomical MRI could potentially improve the diagnosis of PAS disorders in clinical practice.

Level Of Evidence: 2 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27794DOI Listing
June 2021

Identification of genes related to stress affecting thymus immune function in a chicken stress model using transcriptome analysis.

Res Vet Sci 2021 Sep 7;138:90-99. Epub 2021 Jun 7.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China; Henan Key Laboratory for Innovation and Utilization of Chicken Germplasm Resources, Zhengzhou 450046, China. Electronic address:

With the rapid development of the poultry breeding industry and highly intensive production management, the losses caused by stress responses are becoming increasingly serious. To screen candidate genes related to chicken stress and provide a basis for future research on the molecular mechanisms governing the effects of stress on chicken immune function, we successfully constructed a chicken stress model by exogenously introducing corticosterone (CORT). RNA-seq technology was used to identify and analyze the mRNA and enrichment pathways of the thymus in the stress model group and the control group. The results showed that there were 101 significantly differentially expressed genes (SDEGs) (Padj < 0.05, |log2fold changes| ≥ 1 and FPKM >1), of which 44 were upregulated genes, while 57 were downregulated genes. Gene Ontology (GO) enrichment analysis found that the terms related to immunity or stress mainly included antigen processing and presentation, positive regulation of T cell-mediated immunity, and immune effector process. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the main pathways related to immunity or stress were the PPAR signaling pathway, NOD-like receptor signaling pathway, and intestinal immune network for IgA production. Among the SDEGs, XCL1, HSPA8, DMB1 and BAG3 are strongly related to immunity or stress and may be important genes involved in regulating stress affecting the immune function of chickens. The above results provide a theoretical reference for subsequent research on the molecular regulatory mechanisms by which stress affects the immune function of poultry.
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http://dx.doi.org/10.1016/j.rvsc.2021.06.006DOI Listing
September 2021

Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy.

J Nanobiotechnology 2021 Jun 10;19(1):175. Epub 2021 Jun 10.

Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.

Background: Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies.

Methods: We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (Cu-NOTA-DBCO) using bioorthogonal chemistry. Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi).

Results: CTLs can be stably radiolabeled with Cu with a minimal effect on cell viability. PET imaging of Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms.

Conclusion: These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens.
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http://dx.doi.org/10.1186/s12951-021-00924-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194184PMC
June 2021

Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production.

Sci China Life Sci 2021 Jun 4. Epub 2021 Jun 4.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming. Moreover, insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion, reproduction, and meat quality in MSTN-edited pigs have also currently blocked progress. Here, in a largest-to-date evaluation of multiple MSTN-edited pig populations, we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness. We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size. Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production, our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic backgrounds.
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http://dx.doi.org/10.1007/s11427-020-1927-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188954PMC
June 2021

AtWAKL10, a Cell Wall Associated Receptor-Like Kinase, Negatively Regulates Leaf Senescence in .

Int J Mol Sci 2021 May 5;22(9). Epub 2021 May 5.

Tobacco Research Institute, Chinese Academy of Agricultural Sciences, Qingdao 266101, China.

Receptor-like kinases (RLKs) constitute a large group of cell surface receptors that play crucial roles in multiple biological processes. However, the function of most RLKs in plants has not been extensively explored, and much less for the class of cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs). In this study, analyses of developmental expression patterns uncovered a putative role of AtWAKL10 in modulating leaf senescence, which was further investigated at physiological and molecular levels. The expression level of increased with the developmental progression and was rapidly upregulated in senescing leaf tissues. The promoter of contains various defense and hormone responsive elements, and its expression could be significantly induced by exogenous ABA, JA and SA. Moreover, the loss-of-function mutant showed earlier senescence along the course of natural development and accelerated leaf senescence under darkness and hormonal stresses, while plants overexpressing showed an opposite trend. Additionally, some defense and senescence related WRKY transcription factors could bind to the promoter of . In addition, deletion and overexpression of AtWAKL10 caused several specific transcriptional alterations, including genes involved in cell extension, cell wall modification, defense response and senescence related WRKYs, which may be implicated in regulatory mechanisms adopted by AtWAKL10 in controlling leaf senescence. Taken together, these results revealed that AtWAKL10 negatively regulated leaf senescence.
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http://dx.doi.org/10.3390/ijms22094885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124439PMC
May 2021

Mapping fetal brain development based on automated segmentation and 4D brain atlasing.

Brain Struct Funct 2021 Jul 29;226(6):1961-1972. Epub 2021 May 29.

Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang, China.

Fetal brain MRI has become an important tool for in utero assessment of brain development and disorders. However, quantitative analysis of fetal brain MRI remains difficult, partially due to the limited tools for automated preprocessing and the lack of normative brain templates. In this paper, we proposed an automated pipeline for fetal brain extraction, super-resolution reconstruction, and fetal brain atlasing to quantitatively map in utero fetal brain development during mid-to-late gestation in a Chinese population. First, we designed a U-net convolutional neural network for automated fetal brain extraction, which achieved an average accuracy of 97%. We then generated a developing fetal brain atlas, using an iterative linear and nonlinear registration approach. Based on the 4D spatiotemporal atlas, we quantified the morphological development of the fetal brain between 23 and 36 weeks of gestation. The proposed pipeline enabled the fully automated volumetric reconstruction for clinically available fetal brain MRI data, and the 4D fetal brain atlas provided normative templates for the quantitative characterization of fetal brain development, especially in the Chinese population.
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http://dx.doi.org/10.1007/s00429-021-02303-xDOI Listing
July 2021

Copper Preserves Vasculature Structure and Function by Protecting Endothelial Cells from Apoptosis in Ischemic Myocardium.

J Cardiovasc Transl Res 2021 May 17. Epub 2021 May 17.

Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, People's Republic of China.

The present study was undertaken to investigate whether Cu protects vasculatures from ischemic injury in the heart. C57/B6 mice were introduced to myocardial ischemia (MI) by permanent ligation of the left anterior descending (LAD) coronary artery. Two hours post-LAD ligation, mice were intravenously injected with a Cu-albumin (Cu-alb) solution, or saline as control. At 1, 4, or 7 days post-MI, hearts were collected for further analysis. A dramatic decrease in CD31-positive endothelial cells concomitantly with abundant apoptosis, along with obstruction of blood flow, was observed in ischemic myocardium 1 day post-MI. The early Cu-alb treatment protected CD31-positive cells from apoptosis, along with a preservation of micro-vessels and a decrease in infarct size. This early vasculature preservation ensured myocardial blood perfusion and protected cardiac contractile function until 28 days post-MI. This strategy of Cu-alb treatment immediately following MI would help develop a therapeutic approach for acute heart attack patients in a clinical setting.
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http://dx.doi.org/10.1007/s12265-021-10128-6DOI Listing
May 2021

Constructing Ultrathin W-Doped NiFe Nanosheets via Facile Electrosynthesis as Bifunctional Electrocatalysts for Efficient Water Splitting.

ACS Appl Mater Interfaces 2021 May 26;13(17):20070-20080. Epub 2021 Apr 26.

Nanodynamics and High-Efficiency Lab for Propulsion and Power, Department of Mechanical, Aerospace & Biomedical Engineering, UT Space Institute, University of Tennessee, Knoxville, Tullahoma, Tennessee 37388, United States.

Exploring cost-effective and efficient bifunctional electrocatalysts via simple fabrication strategies is strongly desired for practical water splitting. Herein, an easy and fast one-step electrodeposition process is developed to fabricate W-doped NiFe (NiFeW)-layered double hydroxides with ultrathin nanosheet features at room temperature and ambient pressure as bifunctional catalysts for water splitting. Notably, the NiFeW nanosheets require overpotentials of only 239 and 115 mV for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively, to reach a current density of 10 mA/cm in alkaline media. Their exceptional performance is further demonstrated in a full electrolyzer configuration with the NiFeW as both anode and cathode catalysts, which achieves a low cell voltage of 1.59 V at 10 mA/cm, 110 mV lower than that of the commercial IrO (anode) and Pt (cathode) catalysts. Moreover, the NiFeW nanosheets are superior to various recently reported bifunctional electrocatalysts. Such remarkable performances mainly ascribe to W doping, which not only effectively modulates the electrocatalyst morphology but also engineers the electronic structure of NiFe hydroxides to boost charge-transfer kinetics for both the OER and HER. Hence, the ultrathin NiFeW nanosheets with an efficient fabrication strategy are promising as bifunctional electrodes for alkaline water electrolyzers.
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http://dx.doi.org/10.1021/acsami.1c01815DOI Listing
May 2021

Correction: The chromosome-based lavender genome provides new insights into Lamiaceae evolution and terpenoid biosynthesis.

Hortic Res 2021 Apr 15;8(1):90. Epub 2021 Apr 15.

Key Laboratory of Plant Resources and Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, Xiangshan, 100093, Beijing, China.

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http://dx.doi.org/10.1038/s41438-021-00536-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050050PMC
April 2021

The Meishan pig genome reveals structural variation-mediated gene expression and phenotypic divergence underlying Asian pig domestication.

Mol Ecol Resour 2021 Aug 26;21(6):2077-2092. Epub 2021 Apr 26.

State Key Laboratory of Animal Nutrition, Key Laboratory of Animal Genetics Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

There are wide genomic and phenotypic differences between Asian and European pig breeds, yet the current reference genome is the European Duroc pig genome. A high-quality pig genome is lacking for genetic analysis of agricultural traits in Asian pigs. Here, using a hybrid approach, a high-quality reference genome (MSCAAS v1) for the Asian Meishan breed is assembled with a contig N50 size of 48.05 Mb. MSCAAS v1 outperforms the Duroc genome as a reference genome for Asian breeds. Genomic comparison reveals 49,103 structural variations (SVs) between Meishan and Duroc, 4.02% of which are Asian-specific SVs (AP-SVs). Notably, a 30-Mb hotspot for AP-SVs on chromosome X enriched for genes associated with Asian-pig-specific phenotypes is present in Asian domestic pig breeds, but absent in Asian wild boars, suggesting that Asian domestic breeds share a common ancestor. Interbreed transcriptomics reveals transcriptional suppression roles of AP-SVs in multiple tissues. Finally, transcriptional regulation in the intron of IGF2R is reported, as genomic SV (274-bp deletion) in Tibetan pig limits its growth compared to domestic pig breeds. In summary, this study provides insights regarding the genetic changes underlying pig domestication and presents a benchmark-setting resource for the utilization of agricultural valuable loci in Asian pigs.
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http://dx.doi.org/10.1111/1755-0998.13396DOI Listing
August 2021

Identification and expression analysis of MicroRNAs in chicken spleen in a corticosterone-induced stress model.

Res Vet Sci 2021 May 1;136:287-296. Epub 2021 Mar 1.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China. Electronic address:

For investigating the effects of stress on the immune response of chickens, we established a corticosterone (CORT)-induced stress model by exogenous intake of CORT. Control group was fed with a basal diet and the stress model group was fed with a 30 mg/Kg CORT-treated diet in ad libitum conditions for 7 days. Then, we used RNA-seq technology to identify the expression pattern of miRNAs, target genes, and relevant pathways in chicken spleen. Results showed that 71 differentially expressed miRNAs (DEMs) were determined, 9 of which were significantly differentially expressed miRNAs (SDEMs), and 241 target genes of DEMs were predicted. GO annotation and KEGG pathway analysis were carried out to understand the role of the DEMs. Out of 287 significantly enriched GO terms, 37 were stress- or immune-related, such as response to light stimulus, detection of oxidative stress, and immune response in mucosal-associated lymphoid tissue. Out of 85 KEGG pathways, 8 were related to stress or immunity, such as cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, and RLR signaling pathway. We then constructed the interaction networks between target genes from immune-related pathways and their DEMs. The analysis results suggested that some DEMs (gga-miR-17 family, gga-miR-15/16 family, gga-miR-2954 and gga-miR-34b-5p) and target genes (SIKE1, CX3CL1, IL11Ra, PIGR, and CDKN1A) were core miRNAs and genes. This study revealed the dynamic miRNA transcriptome, target genes and related pathways in chicken spleen under CORT-induced stress model, which provided a basis for studying the molecular mechanism of stress affecting immune function.
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http://dx.doi.org/10.1016/j.rvsc.2021.02.023DOI Listing
May 2021

Identification of Protein Direct Interactome with Genetic Code Expansion and Search Engine OpenUaa.

Adv Biol (Weinh) 2021 03 8;5(3):e2000308. Epub 2021 Feb 8.

MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.

Protein crosslinks occur endogenously such as modifications by ubiquitin-like proteins for signaling, or exogenously through genetically encoded chemical crosslinkers (GECX) for studying elusive protein-protein interactions. However, it remains challenging to identify these protein crosslinks efficiently at the proteomic scale. Herein, software OpenUaa is developed for identifying protein crosslinks generated by genetically encoded unnatural amino acids and endogenous protein conjugation. OpenUaa features inclusive and open search capability, dramatically improving identification sensitivity and coverage. Integrating GECX with OpenUaa, the direct interactome of thioredoxin is identified in Escherichia coli cells, yielding 289 crosslinked peptides and corresponding to 205 direct binding protein of thioredoxin. These identified direct binders provide evidence for thioredoxin's regulation of redox state and mitochondria energy metabolism. When identifying endogenous conjugation of small ubiquitin-like modifier (SUMO), OpenUaa also markedly improves coverage of SUMOylated peptides by ≈92%, revealing new SUMO targets. GECX-OpenUaa will enable efficient identification of direct interactomes of various proteins in live cells.
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http://dx.doi.org/10.1002/adbi.202000308DOI Listing
March 2021

Comparison of the application value of two commonly used minimally invasive spinal surgery in the treatment of lumbar disc herniation.

Exp Ther Med 2021 Apr 28;21(4):299. Epub 2021 Jan 28.

Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

The aim of the study was to compare the application value of percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED) in the treatment of lumbar disc herniation (LDH). From January 2017 to July 2018, 108 LDH patients undergoing surgical treatment in our hospital were collected and divided into PTED group (treated with PTED, n=50) and MED group (treated with MED, n=58). The operation parameter index level, complications, recurrence and pain score (VAS), Oswestry disability index (ODI) and Japanese Orthopaedic Association Scale (JOA) were compared between the two groups. VAS, ODI and JOA scores of the two groups were significantly decreased after operation (P<0.05), but there was no significant difference between the two groups (P>0.05). Complications and recurrence of the two groups were similar (P>0.05). MED was superior to PTED in the number of intraoperative fluoroscopy and operation time, while PTED was superior to MED in intraoperative blood loss, incision length, length of hospital stay and bed rest time (P<0.05). Both PTED and MED can effectively treat LDH. Referring to clinical data, PTED may be the first choice for LDH treatment.
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http://dx.doi.org/10.3892/etm.2021.9730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885071PMC
April 2021

Analysis of miRNA and mRNA reveals core interaction networks and pathways of dexamethasone-induced immunosuppression in chicken bursa of Fabricius.

Mol Immunol 2021 06 10;134:34-47. Epub 2021 Mar 10.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Henan Innovative Engineering Research Center of Poultry Germplasm Resource, Zhengzhou 450046, China. Electronic address:

Stress-induced immunosuppression is a serious problem affecting the production value of poultry, but its specific molecular mechanism has not yet been elucidated. We selected 7-day-old Gushi cocks as test animals and successfully established a stress-induced immunosuppression model by injecting 2.0 mg/kg (body weight) dexamethasone (Dex). We then constructed six cDNA libraries and two small RNA libraries of Bursa of Fabricius from the control group and the Dex group. RNA-seq results revealed 21,028 transcripts including 3920 novel transcripts; 500 miRNAs including 68 novel miRNAs were identified. Correlation analysis of miRNA, target genes and mRNA results indicated that the gga-miR-15 family, gga-miR-103-3p, gga-miR-456-3p, and gga-miR-27b-3p, as core differentially expressed miRNAs, may potentially regulate multiple genes which are involved in immune-related pathways; and that the core genes Suppressor of IKBKE 1 (SIKE1) and high mobility group AT-hook 2 (HMGA2) are associated with the miR-17 family (gga-miR-20a-5p, gga-miR-20b-5p, gga-miR-106-5p, and gga-miR-17-5p) and gga-let -7 family (gga-let-7b, gga-let-7i, gga-let-7c-5p, and gga-let-7f-5p). The interaction networks of mRNAs of significantly enrichment pathways and PPI (protein-protein interaction) networks showed that IL6, IL1B, IL8L1, CCL5, SOCS3, SOCS1, ITGB5, GSTA3, SQLE, FDFT1, FN1, IL18, IL10, MAPK11 and MAPK12 are network core nodes and that most of them are strongly associated with immune response. One of the candidate miRNAs, gga-miR-20b-5p, may play an important role in stress-induced immunosuppression. Luciferase assay and over-expression experiments suggested that gga-miR-20b-5p negatively regulated the expression of target gene SIKE1. These results provide better understanding of the mechanism of stress-induced immunosuppression in Gushi chicken bursa, and provide novel targets for subsequent research to improve poultry anti-stress capability.
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http://dx.doi.org/10.1016/j.molimm.2021.02.022DOI Listing
June 2021

Integrated Microbiome and Metabolome Analysis Reveals a Positive Change in the Intestinal Environment of Edited Large White Pigs.

Front Microbiol 2021 17;12:628685. Epub 2021 Feb 17.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

Myostatin (MSTN) functional inactivation can change the proportion of lean meat and fat content in pigs. While both genotype and microbial composition are known to affect the host phenotype, so far there has been no systematic study to detect the changes in the intestinal microbial composition and metabolome of single copy mutant pigs. Here, we used 16S rDNA sequencing and metabolome analysis to investigate how gene editing affects changes in the microbial and metabolome composition in the jejunum and the cecum of Large White pigs. Our results showed that , , , , , and were significantly upregulated; while and were significantly downregulated in the jejunum of MSTN pigs. Similarly, , , , , and were significantly upregulated, while was significantly downregulated in the cecum of MSTN pigs. Moreover, metabolomics analysis showed significant changes in metabolites involved in purine, sphingolipid and tryptophan metabolism in the jejunum, while those associated with glycerophospholipid and pyrimidine metabolism were changed in the cecum. Spearman correlation analysis further demonstrated that there was a significant correlation between microflora composition and metabolites. Our analyses indicated the editing affects the composition of metabolites and microbial strains in the jejunum and the cecum, which might provide more useable nutrients for the host of ± Large White pigs.
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http://dx.doi.org/10.3389/fmicb.2021.628685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925633PMC
February 2021

Highly stable selenium nanoparticles: Assembly and stabilization via flagellin FliC and porin OmpF in Rahnella aquatilis HX2.

J Hazard Mater 2021 07 26;414:125545. Epub 2021 Feb 26.

College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China; Beijing Key Laboratory of Biodiversity and Organic Farming, China Agricultural University, Beijing 100193, China. Electronic address:

Microorganisms play a critical role in the reduction of the more toxic selenite and selenate to the less toxic elemental selenium. However, the assembly process and stability of selenium nanoparticles (SeNPs) remain understudied. The plant growth-promoting rhizobacterium Rahnella aquatilis HX2 can reduce selenite to biogenic SeNPs (BioSeNPs). Two main proteins, namely flagellin FliC and porin OmpF were identified in the BioSeNPs. The fliC and ompF gene mutation experiments demonstrated that the FliC and OmpF could control the assembly of BioSeNPs in vivo. At the same time, the expressed and purified FliC and OmpF could control the assembly of SeNPs in vitro. BioSeNPs produced by R. aquatilis HX2 exhibited high stability under various ionic strengths, while the chemically synthesized SeNPs (CheSeNPs) showed a high level of aggregation. The in vitro experiments verified that FliC and OmpF could prevent the aggregation of the CheSeNPs under various ionic strengths. This work reports the preparation of highly stable BioSeNPs produced by strain R. aquatilis HX2 and verifies that FliC and OmpF both could control the assembly and stability of BioSeNPs. BioSeNPs with high stability could be suitable as nutritional supplement to remedy selenium deficiency and in nanomedicine applications.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125545DOI Listing
July 2021

COMMD1 upregulation is involved in copper efflux from ischemic hearts.

Exp Biol Med (Maywood) 2021 Mar 6;246(5):607-616. Epub 2020 Dec 6.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Copper depletion is associated with myocardial ischemic infarction, in which copper metabolism MURR domain 1 (COMMD1) is increased. The present study was undertaken to test the hypothesis that the elevated COMMD1 is responsible for copper loss from the ischemic myocardium, thus worsening myocardial ischemic injury. Mice (C57BL/6J) were subjected to left anterior descending coronary artery permanent ligation to induce myocardial ischemic infarction. In the ischemic myocardium, copper reduction was associated with a significant increase in the protein level of COMMD1. A tamoxifen-inducible, cardiomyocyte -specific knockout mouse (C57BL/6J) model () was generated using the recombination system. and wild-type littermates were subjected to the same permanent ligation of left anterior descending coronary artery. At the 7th day after ischemic insult, COMMD1 deficiency suppressed copper loss in the heart, along with preservation of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 expression and the integrity of the vascular system in the ischemic myocardium. Corresponding to this change, infarct size of ischemic heart was reduced and myocardial contractile function was well preserved in mice. These results thus demonstrate that upregulation of COMMD1 is at least partially responsible for copper efflux from the ischemic heart. Cardiomyocyte-specific deletion of COMMD1 helps preserve the availability of copper for angiogenesis, thus suppressing myocardial ischemic dysfunction.
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http://dx.doi.org/10.1177/1535370220969844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934151PMC
March 2021

The chromosome-based lavender genome provides new insights into Lamiaceae evolution and terpenoid biosynthesis.

Hortic Res 2021 Mar 1;8(1):53. Epub 2021 Mar 1.

Key Laboratory of Plant Resources and Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, Xiangshan, 100093, Beijing, China.

The aromatic shrub Lavandula angustifolia produces various volatile terpenoids that serve as resources for essential oils and function in plant-insect communication. To better understand the genetic basis of the terpenoid diversity in lavender, we present a high-quality reference genome for the Chinese lavender cultivar "Jingxun 2" using PacBio and Hi-C technologies to anchor the 894.50 Mb genome assembly into 27 pseudochromosomes. In addition to the γ triplication event, lavender underwent two rounds of whole-genome duplication (WGD) during the Eocene-Oligocene (29.6 MYA) and Miocene-Pliocene (6.9 MYA) transitions. As a result of tandem duplications and lineage-specific WGDs, gene families related to terpenoid biosynthesis in lavender are substantially expanded compared to those of five other species in Lamiaceae. Many terpenoid biosynthesis transcripts are abundant in glandular trichomes. We further integrated the contents of ecologically functional terpenoids and coexpressed terpenoid biosynthetic genes to construct terpenoid-gene networks. Typical gene clusters, including TPS-TPS, TPS-CYP450, and TPS-BAHD, linked with compounds that primarily function as attractants or repellents, were identified by their similar patterns of change during flower development or in response to methyl jasmonate. Comprehensive analysis of the genetic basis of the production of volatiles in lavender could serve as a foundation for future research into lavender evolution, phytochemistry, and ecology.
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http://dx.doi.org/10.1038/s41438-021-00490-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917091PMC
March 2021

Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non-small-cell lung cancer.

Bioengineered 2021 12;12(1):791-802

Translational Medicine Research Institute, Guangzhou Huayin Medical Laboratory Center Co., Ltd., Guangzhou, China.

The knowledge of genetic variation in Chinese patients with non-small-cell lung cancer (NSCLC) is still limited. We aimed to profile this genetic variation in 206 Chinese patients with NSCLC using next-generation sequencing. Tumor tissues or whole-blood samples were collected and subjected to whole-exome targeted next-generation sequencing, which included 565 tumor-associated genes, for somatic gene mutation screening and copy number variation (CNV) detection. Potential functions of most commonly mutated genes and genes with CNV were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Atotal of 18,749 mutations were identified using targeted next-generation sequencing, and 85.3% of them were missense mutations. Among the mutation, conversions between pyrimidine and purine were predominant, and C> T/G > A was the most common substitution type. High frequencies of mutations were noted in TP53 (47.6%), EGFR (41.7%), CREBBP (23.1%), KMT2C (16.9%), MUC2 (16.6%), DNMT3A (15.5%), LRP1B (15.5%), MUC4 (15.5%), CDC27 (15.2%), and KRAS (12.8%). EGFR and KRAS mutations were mutually exclusive. The tumor mutation load showed differences depending on gender and tumor type. CNV analysis showed that BCORL1 and ARAF have the highest copy number amplification, whereas KDM6A and RBM10 showed the highest copy number deletion. GO and KEGG analyses indicated that high-frequency mutations and CNV genes were concentrated in tumor-related PI3K-Akt, FoxO, and Ras signaling pathway. Cumulatively, we studied somatic gene mutations involved in NSCLC and predicted their clinical significance in Chinese population. These findings may provide clues for etiology and drug target of NSCLC.
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http://dx.doi.org/10.1080/21655979.2021.1890382DOI Listing
December 2021

Prenatal Diagnosis and Classification of Fetal Hypospadias: The Role and Value of Magnetic Resonance Imaging.

J Magn Reson Imaging 2021 06 19;53(6):1862-1870. Epub 2021 Feb 19.

Department of Radiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Prenatal diagnosis and classification of hypospadias are difficult and of value for management during perinatal and neonatal periods. The conventional approach for prenatal diagnosis of hypospadias is ultrasound; however, this technique may be inconclusive in certain cases, which prompts for further exploration with magnetic resonance imaging (MRI).

Purpose: To investigate the role of MRI in the prenatal diagnosis and classification of fetuses with hypospadias.

Study Type: Retrospective.

Population: Thirty-five fetuses (median gestational age = 37, range 24-39 weeks) with possible hypospadias.

Field Strength/sequence: Single-shot fast spin echo T2-weighted imaging, fast imaging employing steady-state acquisition (FIESTA), and three-dimensional FIESTA acquired at 1.5 T.

Assessment: Diagnosis and classification of hypospadias using MRI were performed by three experienced radiologists based on MRI features, including a short penile shaft, abnormal penile tip, penile curvature, bifid scrotum, "tulip sign," and penoscrotal transposition. The accuracy of MRI in the diagnosis and classification of hypospadias was assessed in comparison to postnatal clinical diagnosis. The interobserver agreement between radiologists was also assessed.

Statistical Tests: Kendall's W test was applied to assess the interobserver agreement between radiologists. Taking postnatal clinical diagnosis as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated.

Results: Of the 35 fetuses, 24 cases were confirmed as hypospadias through postnatal clinical diagnosis. The interobserver agreement between radiologists was substantial (Kendall's W = 0.781, P < 0.001). Of the 24 confirmed cases (13 cases of severe hypospadias and 11 cases of mild hypospadias), 22 cases were correctly diagnosed by MRI. The accuracy of MRI in the diagnosis of hypospadias, severe hypospadias, and mild hypospadias was 85.71%, 82.86%, and 80.00%, respectively.

Data Conclusion: MRI has good performance in the diagnosis of fetal hypospadias. In addition, MRI could help evaluate the severity of fetal hypospadias.

Level Of Evidence: 3 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27519DOI Listing
June 2021

In Situ Synthesis of Lead-Free Halide Perovskite CsAgBiBr Supported on Nitrogen-Doped Carbon for Efficient Hydrogen Evolution in Aqueous HBr Solution.

ACS Appl Mater Interfaces 2021 Mar 19;13(8):10037-10046. Epub 2021 Feb 19.

Department of Chemistry, National University of Singapore (NUS), Singapore 117543, Singapore.

Lead halide perovskites have shown great potential in photovoltaic and photocatalytic fields. However, the toxicity of lead impedes their wide application. Herein composites of lead-free halide perovskite CsAgBiBr supported on nitrogen-doped carbon (N-C) materials were synthesized successfully through a facile one-pot method for the first time. Without deposition of noble metals as the cocatalyst, the optimal composite CsAgBiBr/N-C (CsAgBiBr/N-C-140) exhibits outstanding photocatalytic performance with a high hydrogen evolution rate of 380 μmol g h under visible light irradiation (λ ≥ 420 nm), which is about 19 times faster than that of pure CsAgBiBr and 4 times faster than that of physically mixed CsAgBiBr/N-C-140, respectively. The CsAgBiBr/N-C-140 composite also displays high stability with no significant decrease after six cycles of repeated hydrogen evolution experiments. The addition of N-C with a high surface area helps to prevent aggregation of CsAgBiBr NPs and provides more pathways for the migration of photoinduced carriers. The nitrogen dopant can facilitate photoinduced electron transfer from CsAgBiBr to N-C to result in spatially separated electrons and holes with prolonged electron time and greatly enhance the photocatalytic performance. This study indicates that CsAgBiBr-based perovskite materials are promising candidates for photocatalytic hydrogen evolution.
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http://dx.doi.org/10.1021/acsami.0c21588DOI Listing
March 2021

Polycysteine as a new type of radio-protector ameliorated tissue injury through inhibiting ferroptosis in mice.

Cell Death Dis 2021 02 18;12(2):195. Epub 2021 Feb 18.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, 300000, Tianjin, China.

Amifostine has been the only small molecule radio-protector approved by FDA for decades; however, the serious adverse effects limit its clinical use. To address the toxicity issues and maintain the good potency, a series of modified small polycysteine peptides had been prepared. Among them, compound 5 exhibited the highest radio-protective efficacy, the same as amifostine, but much better safety profile. To confirm the correlation between the radiation-protective efficacy and the DNA binding capability, each of the enantiomers of the polycysteine peptides had been prepared. As a result, the L-configuration compounds had obviously higher efficacy than the corresponding D-configuration enantiomers; among them, compound 5 showed the highest DNA binding capability and radiation-protective efficacy. To our knowledge, this is the first study that has proved their correlations using direct comparison. Further exploration of the mechanism revealed that the ionizing radiation (IR) triggered ferroptosis inhibition by compound 5 could be one of the pathways for the protection effect, which was different from amifostine. In summary, the preliminary result showed that compound 5, a polycysteine as a new type of radio-protector, had been developed with good efficacy and safety profile. Further study of the compound for potential use is ongoing.
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http://dx.doi.org/10.1038/s41419-021-03479-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977147PMC
February 2021

Draft genome of the herbaceous bamboo Raddia distichophylla.

G3 (Bethesda) 2021 02;11(2)

Institution of Genomics and Bioinformatics, South China Agricultural University, Guangzhou 510642, China.

Bamboos are important nontimber forest plants widely distributed in the tropical and subtropical regions of Asia, Africa, America, and Pacific islands. They comprise the Bambusoideae in the grass family (Poaceae), including approximately 1700 described species in 127 genera. In spite of the widespread uses of bamboo for food, construction, and bioenergy, the gene repertoire of bamboo still remains largely unexplored. Raddia distichophylla (Schrad. ex Nees) Chase, belonging to the tribe Olyreae (Bambusoideae, Poaceae), is a diploid herbaceous bamboo with only slightly lignified stems. In this study, we report a draft genome assembly of the ∼589 Mb whole-genome sequence of R. distichophylla with a contig N50 length of 86.36 Kb. Repeat sequences account for ∼49.08% of the genome assembly, of which LTR retrotransposons occupy ∼35.99% of the whole genome. A total of 30,763 protein-coding genes were annotated in the R. distichophylla genome with an average transcript size of 2887 bp. Access to this herbaceous bamboo genome sequence will provide novel insights into biochemistry, molecular marker-assisted breeding programs, and germplasm conservation for bamboo species worldwide.
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http://dx.doi.org/10.1093/g3journal/jkaa049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022951PMC
February 2021

Genetic Dissection of the Regulatory Mechanisms of in the Infected Mouse Lung.

Front Immunol 2020 8;11:607314. Epub 2021 Jan 8.

Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, United States.

Acute lung injury (ALI) is an important cause of morbidity and mortality after viral infections, including influenza A virus H1N1, SARS-CoV, MERS-CoV, and SARS-CoV-2. The angiotensin I converting enzyme 2 (ACE2) is a key host membrane-bound protein that modulates ALI induced by viral infection, pulmonary acid aspiration, and sepsis. However, the contributions of sequence variants to individual differences in disease risk and severity after viral infection are not understood. In this study, we quantified H1N1 influenza-infected lung transcriptomes across a family of 41 BXD recombinant inbred strains of mice and both parents-C57BL/6J and DBA/2J. In response to infection mRNA levels decreased significantly for both parental strains and the expression levels was associated with disease severity (body weight loss) and viral load (expression levels of viral NA segment) across the BXD family members. Pulmonary RNA-seq for 43 lines was analyzed using weighted gene co-expression network analysis (WGCNA) and Bayesian network approaches. not only participated in virus-induced ALI by interacting with TNF, MAPK, and NOTCH signaling pathways, but was also linked with high confidence to gene products that have important functions in the pulmonary epithelium, including , , and . Comparable sets of transcripts were also highlighted in parallel studies of human SARS-CoV-infected primary human airway epithelial cells. Using conventional mapping methods, we determined that weight loss at two and three days after viral infection maps to chromosome X-the location of . This finding motivated the hierarchical Bayesian network analysis, which defined molecular endophenotypes of lung infection linked to expression and to a key disease outcome. Core members of this Bayesian network include , , , , , , , and . Collectively, these findings define a causally-rooted modulatory network relevant to host response to viral infection and identify potential therapeutic targets for virus-induced respiratory diseases, including those caused by influenza and coronaviruses.
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http://dx.doi.org/10.3389/fimmu.2020.607314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819859PMC
February 2021

Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity.

Reprod Biol Endocrinol 2021 Jan 7;19(1). Epub 2021 Jan 7.

College of Animal Science, Zhejiang University, 866 Yuhangtang Road, 310058, Hangzhou, P. R. China.

Background: The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated.

Methods: ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors.

Results: ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19.

Conclusion: These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton.
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http://dx.doi.org/10.1186/s12958-020-00689-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788769PMC
January 2021
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